What are three immune complications possible with transplant
Rejection, Infection, Malignancy
What do high levels of AST and ALT relate to the function which organ?
What are the different type of organ rejection?
-Acute Early (CD8-driven)
-Acute Late (CD-4 driven)
Describe Hyperacute Rejection
1. Pre-existing Ab's bind onto donor Ag's
2. These Ab's allow for activation of complement
3. Complement leads to inflammation
4. Result is thrombosis
List the important characteristics of early vs. late acute rejection
-Days to weeks after transpllant
-Early rejection involves CTLs
-CTLs react to donor APC presenting donor Ag on MHC I
-Months to years after transplant
Th1 mediated CD4+
-T cells responding to recipient ACP presenting donor Ag on MHC II
In which organs is hyperacute rejection most common?
Lung, Kidney, Heart
With transplant surgery, these is alot of damage. Describe how that damage manifests an immune response
DAMPS (Hsp70, polysaccharide fragments from heparin sulfate, HMBG1/Rage, Fibrinogen) --> PPR (TLRs, CLRs, NODs, BLRs, RLRs) --> Innate immune system --> inflammation, complement, leukocyte recruitment, clearance and killing, and adaptive immunity
Differentiate between direct and indirect activation of the host immune system
Direct: The donor APC presents donor Ag on MHC class I to host CD8+ Cells
Indirect: The host APC presents donor Ag on MHC class I to host CD4+ T cells
Is it possible for acute rejection to display a mixtube of both CD4+ and CD8+ cellular infiltrate?
Yes, this can make classification difficult
If you have a patient who present with both histologically and biochemically acute rejection, what is the first line treatment?
Steroids, the side effects suck though
What is chronic rejection exemplified by?
Duct loss and less inflammation, more fibrosis
If steroids dont work, then what?
Anti-thymocyte Globulins (bind and sequester, can lead to destruction) - this is basically an anti-T cell drug, it is a polyclonal antibody against numerous lymphocyte markers that will eithe inhibit or destory T-cells
Which two drugs inhibit activation of calcineurin?
Cyclophosphamide and Tacrolimus
What is the mechanism of sirolimus?
Helps block signaling through IL-2R, thus preventing replication that is induced by IL-2, like T-cells
What is this?
-actually looks pretty good though, because there is no attack on the bilary ducts
What does PTLD stand for? What type of infection is it most commonly associated with?
Post-Transplant Lymphoproliferative Disorder: reactivation or primary infection of EBV
PTLD happens why?
Since we use immunosuppressant, the pateients CTLs are not able to do enough immune survellience and so virus has free raign, so do tumors
How do you trat PTLD?
1. reduce immunosuppression
2. Ab therapy vs. B cells like Rituximab
4. Adoptive T cell therapy
5. antibiral agents are relatively limited
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